Development of an effective vehicle for cancer gene therapy using novel multigenic vectors is proposed. Liposomes are safe and promising nonviral vehicles for gene therapy. However, their use is limited by specificity. The goal of this proposal is to develop novel targeted liposome-based delivery vehicles for the above vectors. Focusing on the EGF family of receptors which are frequently overexpressed in cancers of epithelial origin, natural ligands will be attached to a common phospholipid component of cationic liposomes and the ability tested of these ligands to specifically direct the liposome carrier to breast cancer cell lines. Transfection efficiency of different liposome mixtures will be tested. In subsequent phases, the most efficient system will be selected for in vivo studies. The ultimate goal is to develop targeted ligand-linked liposomes for systemic administration of therapeutic genes into cancer patients. PROPOSED COMMERCIAL APPLICATION: The proposed research will lead to the development of targeted nonviral gene delivery vehicles to overcome a major barrier to in vivo gene delivery which is lack of specificity. The commercial applications are widespread, ranging from gene therapy, particularly in cancer, as well as in any basic research procedure that requires in vivo transfection to specific cell types.